Cancer Letters
Volume 203, Issue 2 , Pages 145-154, January 2004

TNF-α-mediated apoptosis in normal human prostate epithelial cells and tumor cell lines

  • Dharam P. Chopra

      Affiliations

    • Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48201, USA
    • Corresponding Author InformationCorresponding author. Address: Institute of Environmental Health Sciences, Wayne State University, 2727 Second Avenue, Room 4000, Detroit, MI 48201, USA. Tel.: +1-313-961-2816; fax: +1-313-577-0082
    • ,
  • Raymond E. Menard

      Affiliations

    • Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA
    • ,
  • Jakub Januszewski

      Affiliations

    • Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48201, USA
    • Present address: 1200 Academy Street, Hicks Center Box 375, Kalamazoo, MI 49006, USA.
    • ,
  • Raymond R. Mattingly

      Affiliations

    • Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA

Received 27 June 2003; received in revised form 23 September 2003; accepted 24 September 2003.

Abstract 

In this study we compared the role of TNF-α in the regulation of growth and apoptosis in normal human prostate epithelial cells (NP) and prostate tumor cell lines PC3 and LNCap. The NP and PC3 cells were resistant whereas the LNCap cell line was highly sensitive to TNF-α induced growth arrest and apoptosis. The resistance of NP and PC3 cells was mediated via an NF-kB survival pathway as treatment of resistant cells with TNF-α was accompanied by phosphorylation of I-kBα and translocation of NF-kB to the nucleus. TNF-α did not induce phosphorylation of I-kB in the sensitive LNCap cells. The sensitivity of LNCap cells involved a cysteine protease cascade as Z-VAD-CH2 F reversed the sensitivity of LNCap cells and induced resistance to TNF-α. The differences in susceptibilities to TNF-α induced apoptosis of NP and certain prostate tumor cells offer intriguing possibilities for the treatment of prostate cancer without affecting the normal prostate tissue.

Keywords: Human prostate, Normal epithelial cells, Apoptosis, Growth

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PII: S0304-3835(03)00658-X

doi:10.1016/j.canlet.2003.09.016

Cancer Letters
Volume 203, Issue 2 , Pages 145-154, January 2004

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